Mechanisms underpinning the dysfunctional immune response in SARS-CoV-2 infection are not yet fully understood. In addition, the functional roles of the genetic variants identified by COVID-19 ...genome-wide association study (GWAS) remain elusive, especially in non-European ancestry. We analyzed single-cell transcriptomes and T and B cell receptors of > 895,000 peripheral blood mononuclear cells from 73 COVID-19 patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19, suggesting that the dysfunction of ncMono might be closely involved in the immunopathology of COVID-19 severity. Clonal expansions of B cell receptors were evident in plasmablasts of patients. Putative disease genes identified by the GWAS of severe phenotypes showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had COVID-19-specific and monocyte-specific expression quantitative trait loci effects, indicating the enrichment of host genetic risk in innate immune cells. Our multimodal and integrative single-cell analyses highlight biological and host genetic involvement of innate immune cells in COVID-19 severity.
PURPOSETo report anterior chamber flare using laser flare photometry and ciliochoroidal detachment using anterior segment optical coherence tomography (AS-OCT) in a new onset acute lupus ...choroidopathy case. OBSERVATIONSA 57-year-old woman with severe nephritis, pleural effusion, and ascites was referred to our ophthalmology clinic for rapid onset of bilateral blurred vision and eyelid swelling. She had a bilateral high-flared, shallow anterior chamber, and bilateral ciliochoroidal detachment, which was revealed using laser flare photometry and AS-OCT. She also had a serous retinal detachment and disc-macular retinoschisis with a thicker choroid and waved Bruch's membrane. Indocyanine green angiography (ICGA) demonstrated partial hypocyanescence in the early phase and multiple hypercyanescent spots at the intermediate to late phase, which are typical of lupus choroidopathy. Systemic lupus erythematosus was diagnosed, and after the administration of pulse methylprednisolone and pulse cyclophosphamide therapies, all eye findings completely resolved in a month, and all other signs and symptoms improved. CONCLUSIONS AND IMPORTANCELupus choroidopathy, which is less common than retinopathy, might be under-diagnosed because of its difficult evaluation. Although ICGA is the gold standard for diagnosing lupus choroidopathy, a high flare of the anterior chamber and ciliochoroidal detachment might be different from lupus retinopathy. Laser flare photometry and AS-OCT can be non-invasive, helpful tools for the longitudinal evaluation of the patient's response to therapy.
Adult-onset Still's disease (AOSD) is a rare inflammatory autoimmune disorder characterized by fever, skin rash, and arthralgia. Pulmonary artery hypertension (PAH) rarely occurs with AOSD and has ...not been reported in the absence of typical symptoms of AOSD. A 33-year-old woman was admitted to our hospital with dyspnoea on exertion. Although she had not had symptoms of AOSD for 18 months before her admission, she presented with gradually progressing PAH. Because she had no typical symptoms of AOSD, she was treated with pulmonary vasodilators. However, her PAH did not improve. At one month after vasodilator treatment, she developed a high fever with elevation of ferritin. We determined that her AOSD had relapsed. Immunosuppressants were started and both her AOSD and PAH quickly improved. PAH may develop in the absence of typical symptoms of AOSD and immunosuppressants may be effective in such a case.
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